The technical field of this invention is devices and methods useful for the treatment of diseases characterized by the deficiency or lack of essential biologically active molecules and, in particular, implantable and extracorporeal devices for the constitutive delivery of such molecules.
Many diseases or conditions of the body are the result of deficiencies in biologically active molecules or factors, such as enzymes, hormones, neurotransmitters, growth factors, and lymphokines which are normally produced by living cells and which are critical in affecting a requisite change in a target tissue or region of the body. Such diseases and conditions include hypoparathyroidism, immune deficiency syndromes, diabetes mellitus, myxedema, Parkinson's disease, and slow bone growth and mending.
One possible remedy for such deficiency diseases is the direct administration of the deficient molecule to the subject. For example, diabetes mellitus has been treated by the administration of insulin. Similarly, the clinical symptoms of Parkinson's disease, a condition characterized by a deficiency of the neurotransmitter, dopamine, have been improved by the systemic administration of the precursors or agonists of dopamine. See, Calne et al. Lancet ii:973-976 (1969) and Calne et al. Bri, Med. J. 4:442-444 (1974). Moreover, treatment of patients having Acquired Immune Deficiency Syndrome with synthetic thymic hormone (TP5) or with thymosin fraction 5 has been reported to lead to the recovery of T lymphocytes proliferation and function, as well as transient clinical improvement. See, Mascart-Lemone et al. Lancet ii:735-736 (1984) and Rubenstein et al. J. Ped. 103:422-427 (1986).
For this type of treatment, systemic administration by bolus injection is the most common mode of administration. Other techniques include the implantation of slow-release capsules containing the factor as disclosed in U.S. Pat. No. 4,324,683 and continuous administration by pumping mechanisms, such as disclosed in U.S. Pat. Nos. 4,373,527; 4,360,019; and 4,395,259).
However, the identification of the deficiency and the synthesis or isolation of the factor in a form which is stable, pure, and biologically active can be expensive, time-consuming, and difficult. In addition, other problems may be encountered pertaining to determining the appropriate dosage and mode of administration. Also, the recoveries decline upon cessation of the treatment, necessitating long-term, continuous therapy.
An alternative mode of therapy has been to augment or replace the absent or dysfunctional tissue with viable tissue capable of providing the necessary factor. However, prior attempts to do so in a variety of deficiency disorders have often proven to be unsuccessful because of immune reactions (in cases where foreign tissue was utilized) or microbial assault. One solution to this problem disclosed, for example, in U.S. Pat. Nos. 4,391,909 and 3,093,831, has been to encapsulate the factor-producing cells within protective membranes which allow the free diffusion of active factor and nutrients while excluding hostile elements from passage. However, once placed in the body, these encapsulated cells can have a limited life span. Artificial implantable glands with replaceable or replenishable cell cultures have also been developed to solve this problem (as disclosed in U.S. Pat. Nos. 4,242,459; 4,402,694; and 4,378,016), but such devices often have been sluggish in delivering the needed biological factors.
There exists a need for improved therapies for diseases characterized by a deficiency in an active factor in general, and in particular, a need for systems which can augment or replace the functions of dysfunctional glands or tissues of the body. More specifically, there exists a need for a method of providing an active factor to a localized region of the body of a subject deficient or requiring this factor, the correct dosage of which will be constitutively and expeditiously delivered over time.
Accordingly, it is an object of the present invention to provide devices and methods for delivering an active factor to a subject deficient in or in need of that factor and to provide methods of delivering such a factor safely and expeditiously to a localized region of the body of that subject. It is another object of the present invention to provide devices for, and methods of, delivering active factors quickly and in a manner constitutively responsive to the internal environmental requirements of the subject. It is yet another object of the invention to provide an active factor to a subject, the source of which is relatively small, compact, and which requires little surgical maintenance. A further object of the invention is to provide cell culture devices which protect the cells therein from immunological, bacterial, and viral assault, while allowing the delivery of an active factor therefrom.